Structural DNA helical parameters from MD trajectory tutorial using BioExcel Building Blocks (biobb)

Based on the NAFlex server and in particular in its Nucleic Acids Analysis section.


This tutorial aims to illustrate the process of extracting structural and dynamical properties from a DNA MD trajectory helical parameters, step by step, using the BioExcel Building Blocks library (biobb). The particular example used is the Drew Dickerson Dodecamer sequence -CGCGAATTCGCG- (PDB code 1BNA). The trajectory used is a 500ns-long MD simulation taken from the BigNASim database (NAFlex_DDD_II entry).


Settings

Biobb modules used

Auxiliar libraries used

Conda Installation and Launch

git clone https://github.com/bioexcel/biobb_wf_dna_helparms.git
cd biobb_wf_dna_helparms
conda env create -f conda_env/environment.yml
conda activate biobb_dna_helparms_tutorial
jupyter-nbextension enable --py --user widgetsnbextension
jupyter-notebook biobb_wf_md_setup/notebooks/biobb_dna_helparms_tutorial.ipynb

Pipeline steps

  1. Input Parameters
  2. Running Curves+ and Canal
  3. Average Helical Parameters
    1. Base Pair Step (Inter Base Pair) Parameters
    2. Base Pair (Intra Base Pair) Parameters
    3. Axis Parameters
    4. Grooves
    5. Backbone Torsions
  4. Time Series Helical Parameters
  5. Stiffness
  6. Bimodality
  7. Correlations
    1. Sequence Correlations: Intra-base pairs
    2. Sequence Correlations: Inter-base pair steps
    3. Helical Parameter Correlations: Intra-base pairs
    4. Helical Parameter Correlations: Inter-base pair steps
    5. Neighboring steps Correlations: Intra-base pairs
    6. Neighboring steps Correlations: Inter-base pair steps
  8. Questions & Comments

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Input parameters

Input parameters needed:

Running Curves+ and Canal


Curves+ program and its associated Canal tool allow us to extract helical parameters from a DNA MD simulation.

Curves+ is a nucleic acid conformational analysis program which provides both helical and backbone parameters, including a curvilinear axis and parameters relating the position of the bases to this axis. It additionally provides a full analysis of groove widths and depths. Curves+ can also be used to analyse molecular dynamics trajectories. With the help of the accompanying program Canal, it is possible to produce a variety of graphical output including parameter variations along a given structure and time series or histograms of parameter variations during dynamics.

Conformational analysis of nucleic acids revisited: Curves+
R. Lavery, M. Moakher, J. H. Maddocks, D. Petkeviciute, K. Zakrzewska
Nucleic Acids Research, Volume 37, Issue 17, 1 September 2009, Pages 5917–5929
https://doi.org/10.1093/nar/gkp608

CURVES+ web server for analyzing and visualizing the helical, backbone and groove parameters of nucleic acid structure.
R. Lavery, M. Moakher, J.H. Maddocks, D. Petkeviciute, K. Zakrzewska.
Nucleic Acids Res 2009, 37:5917-5929
https://bisi.ibcp.fr/tools/curves_plus/


Building Blocks used:


The extraction of helical parameters is then done in two steps:


Step 1: Curves+

Curves+ program needs a trajectory and its associated topology, and a couple of ranges, informing about the numeration of the two DNA strands: s1range and s2range.

Step 2: Canal

Canal program needs the output of the previous Curves+ execution, and is able to produce time series (series property) and histograms (histo property) for the parameter variations during dynamics.

Extracting Canal results in a temporary folder

Extracting Average Helical Parameters

Average helical parameter values can be computed from the output of Curves+/Canal execution.

The helical parameters can be divided in 5 main blocks:

Helical Base Pair Step (Inter Base Pair) Parameters

Translational (Shift, Slide, Rise) and rotational (Tilt, Roll, Twist) parameters related to a dinucleotide Inter-Base Pair (Base Pair Step).


Helical Base Pair Step Parameters


Building Block used:


Extracting a particular Helical Parameter: Rise

Showing the calculated average values for Rise helical parameter

Plotting the average values for Rise helical parameter

Computing average values from all base-pair step parameters

Showing the calculated average values for all base-pair step helical parameters

Plotting the average values for all base-pair step helical parameters

Helical Base Pair (Intra Base Pair) Parameters

Translational (Shear, Stretch, Stagger) and rotational (Buckle, Propeller, Opening) parameters related to a dinucleotide Intra-Base Pair.


Helical Base Pair Parameters


Building Block used:


Computing average values from all base-pair parameters

Showing the calculated average values for all base-pair helical parameters

Plotting the average values for all base-pair helical parameters

Axis Base Pair Parameters


Translational (x/y-displacement) and rotational (inclination, tip) parameters related to a dinucleotide Base Pair.


Axis Base Pair Parameters


Building Block used:


Computing average values from all Axis base-pair parameters

Showing the calculated average values for all Axis base-pair helical parameters

Plotting the average values for all Axis base-pair helical parameters

Grooves


Nucleic Acid Structure's strand backbones appear closer together on one side of the helix than on the other. This creates a Major groove (where backbones are far apart) and a Minor groove (where backbones are close together). Depth and width of these grooves can be mesured giving information about the different conformations that the nucleic acid structure can achieve.


Grooves Parameters


Building Block used:


Computing average values from all Grooves parameters

Showing the calculated average values for all Grooves parameters

Plotting the average values for all Grooves helical parameters

Backbone Torsions


The three major elements of flexibility in the backbone are:

Sugar Puckering Canonical Alpha/Gamma BI/BII population

Sugar Puckering

Canonical Alpha/Gamma

BI/BII population


Building Blocks used:


Sugar Puckering

Computing average values
Showing the calculated average values
Plotting the average values

Canonical Alpha/Gamma

Computing average values
Showing the calculated average values
Plotting the average values

BI/BII Population

Computing average values
Showing the calculated average values
Plotting the average values

Extracting Time series Helical Parameters

Time series values for the set of helical parameters can be also extracted from the output of Curves+/Canal execution on Molecular Dynamics Trajectories. The helical parameters can be divided in the same 5 main blocks previously introduced:


Building Block used:


Extracting a particular Helical Parameter

Time series values can be extracted from any of the helical parameters previously introduced. To illustrate the steps needed, the base-pair step helical parameter Twist has been selected. Please note that computing the time series values for a different helical parameter just requires modifying the helpar variable from the next cell.

Extracting time series results for the selected helical parameter in a temporary folder

Finding out all the possible nucleotide / base / base-pair / base-pair steps

Discover all the possible nucleotide / base / base-pair / base-pair steps from the sequence. The unit will depend on the helical parameter being studied.
Select one of them to study the time series values of the helical parameter along the simulation.

Showing the time series values for the selected unit

Plotting the time series values for the selected base-pair step

Computing timeseries for all base-pair step parameters

Computing timeseries for all base-pair parameters

Computing timeseries for all axis parameters

Computing timeseries for all grooves parameters

Computing timeseries for all backbone torsions parameters

Stiffness

Molecular stiffness is an elastic force constant associated with helical deformation at the base pair step level and is determined by inversion of the covariance matrix in helical space, which yields stiffness matrices whose diagonal elements provide the stiffness constants associated with pure rotational (twist, roll and tilt) and translational (rise, shift and slide) deformations within the given step.


Stiffness Matrix


Building Blocks used:


Bimodality

Base-pair steps helical parameters usually follow a normal (Gaussian-like) distribution. However, recent studies observed bimodal distributions in some base-pair steps for twist and slide, highlighting potential caveats on the harmonic approximation implicit in elastic analysis and mesoscopic models of DNA flexibility.


Twist bimodality


μABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA
Marco Pasi, John H Maddocks, David Beveridge, Thomas C Bishop, David A Case, Thomas Cheatham 3rd, Pablo D Dans, B Jayaram, Filip Lankas, Charles Laughton, Jonathan Mitchell, Roman Osman, Modesto Orozco, Alberto Pérez, Daiva Petkevičiūtė, Nada Spackova, Jiri Sponer, Krystyna Zakrzewska, Richard Lavery
Nucleic Acids Research 2014, Volume 42, Issue 19, Pages 12272-12283
https://doi.org/10.1093/nar/gku855

Exploring polymorphisms in B-DNA helical conformations
Pablo D Dans, Alberto Pérez, Ignacio Faustino, Richard Lavery, Modesto Orozco
Nucleic Acids Research 2012, Volume 40, Issue 21, Pages 10668-10678
https://doi.org/10.1093/nar/gks884

A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA
Lavery R, Zakrzewska K, Beveridge D, Bishop TC, Case DA, Cheatham T, III, Dixit S, Jayaram B, Lankas F, Laughton C, John H Maddocks, Alexis Michon, Roman Osman, Modesto Orozco, Alberto Perez, Tanya Singh, Nada Spackova, Jiri Sponer
Nucleic Acids Research 2010, Volume 38, Pages 299–313
https://doi.org/10.1093/nar/gkp834


Building Block used:


Correlations

Sequence-dependent correlation movements have been identified in DNA conformational analysis at the base pair and base pair-step level. Trinucleotides were found to show moderate to high correlations in some intra base pair helical parameter (e.g. shear-opening, shear-stretch, stagger-buckle). Similarly, some tetranucleotides are showing strong correlations in their inter base pair helical parameters (e.g. shift-tilt, slide-twist, rise-tilt, shift-slide, and shift-twist in RR steps), with negative correlations in the shift-slide and roll-twist cases. Correlations are also observed in the combination of inter- and intra-helical parameters (e.g. shift-opening, rise-buckle, stagger-tilt). Correlations analysis can be also extended to neighboring steps (e.g. twist in the central YR step of XYRR tetranucleotides with slide in the adjacent RR step).


Rise correlations


The static and dynamic structural heterogeneities of B-DNA: extending Calladine–Dickerson rules
Pablo D Dans, Alexandra Balaceanu, Marco Pasi, Alessandro S Patelli, Daiva Petkevičiūtė, Jürgen Walther, Adam Hospital, Genís Bayarri, Richard Lavery, John H Maddocks, Modesto Orozco Nucleic Acids Research 2019, Volume 47, Issue 21, Pages 11090-11102
https://doi.org/10.1093/nar/gkz905


Building Blocks used:


Sequence Correlations: Intra-base pairs

Sequence Correlations: Inter-base pair steps

Helical Parameter Correlations: Intra-base pair

Helical Parameter Correlations: Inter-base pair steps

Neighboring steps Correlations: Intra-base pair

Neighboring steps Correlations: Inter-base pair steps


Questions & Comments

Questions, issues, suggestions and comments are really welcome!